sepsis, endothelial function, and lipids in critically ill patients with liver failure (the sellifa study)

Conditions: Liver Diseases; Liver Cirrhosis; Sepsis; Critical Illness

Summary: the purpose of the study is to determine the role of new biomarkers in the diagnosis of sepsis in critically-ill patients with liver failure and to correlate the prognosis of these patients with parameters of endothelial function and lipid metabolism.

early diagnosis of sepsis may be difficult in patients with severe liver failure in the absence of usual warning clinical signs. furthermore, routine laboratory tests like blood leucocyte count and serum c-reactive protein may be misleading in most of these patients. a great interest is taken in the identification of sepsis biomarkers or sepsis-induced alterations in the inflammation cascade, whose expression is independent of liver function. determination of such a biomarker may be a useful tool for the early diagnosis of sepsis and may have a prognostic significance in patients with liver failure. septic complications in patients with liver failure may induce a disruption of liver microcirculation, which is regulated by several factors acting on endothelial and liver stellate cells. furthermore, generation of reactive oxygen species results in an oxidative stress on lipids, proteins, and dna. lipid peroxidation may contribute to further hepatocellular injury and activation of systemic inflammation cascade. both endothelial dysfunction and alterations in lipid metabolism may have a role in the prognosis of liver disease and its complications. the purpose of this prospective observational study is to determine the role of new biomarkers in the diagnosis of sepsis in critically-ill patients with liver failure and to correlate the prognosis of these patients with parameters of endothelial function and lipid metabolism. in addition, the porto-systemic gradient of these parameters will be determined in patients planned for a transjugular intra-hepatic porto-systemic shunt (tipss). an overall number of 120 patients will be enrolled. according to the mode of presentation, the planned number of patients in the different study groups will be as follow : 70 patients with chronic liver failure and acute on chronic liver failure; 20 patients with acute liver failure ; 30 patients post-liver transplantation.

Eligibility criteria:
inclusion criteria : * all consecutive patients with a diagnosis of chronic liver failure, acute on chronic liver failure, acute liver failure, or post-liver transplantation ; * adult patient aged 18 years or above, and less than 85 ; * admission to the icu for an expected period of \> 24 hours or elective admission for tipss placement ; * informed consent of the patient or nearest relative. exclusion criteria : * age less than 18 years and more than 85 ; * pregnancy, including hellp syndrome ; * active malignancy with metastases (localised hepatocellular carcinoma is not an exclusion criteria); * systemic chemotherapy in the last 4 weeks (trans-arterial chemo-embolisation for localised hepatocellular carcinoma is not an exclusion criteria) ; * acquired immunodeficiency syndrome and antiretroviral therapy ; * refusal of the patient or nearest relative.

Keywords: liver cirrhosis acute liver failure liver transplantation sepsis, infection endothelium lipids diagnosis prognosis